N-acetyl cysteine (NAC) is made from the amino acid L-cysteine. It is a source of sulfhydryl (-SH) groups and, thus, may act as a strong antioxidant.

Because it has the ability to thin mucus, NAC has been used traditionally as a decongestant. It has also been used to reduce poisoning associated with compounds such as acetaminophen and heavy metals.

NAC has been used clinically for approximately 40 years and has shown benefit for treating bronchiolitis and chronic bronchitis. Recent study has investigated its role as an antioxidant with the potential to treat HIV infection, cancer, and heart conditions. There is a lack of evidence of benefit in using NAC to prevent kidney impairment or to treat hepatitis, cystic fibrosis, or erythropoietic protoporphyria (a disorder caused by a defect in making heme).

NAC is generally well tolerated. The most frequent side effects are diarrhea, nausea, and vomiting. NAC is also well known for its unpleasant taste.

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

GRADE *

Strong scientific evidence supports the use of N-acetyl cysteine (NAC) as an antidote to acetaminophen overdose.

A

NAC is commonly used for lung infections and sputum (phlegm and mucus) clearance. In human study, NAC reduced symptoms in patients with sulfur mustard-induced bronchiolitis (swelling in the small air passages of the lungs). Additional study is needed before a conclusion can be made.

B

NAC has been used to treat chronic bronchitis since the 1960s. Evidence from some human studies suggests that NAC may benefit patients with chronic bronchitis. Other studies show a lack of benefit. Further study is required before firm conclusions can be made.

Preliminary studies suggest that NAC may benefit patients with acute respiratory infections. Because the patients studied were also taking other medications, additional studies testing the effect of NAC alone are needed.

C

In preliminary study, NAC appeared to decrease measures of pathological gambling. Further well-designed research is required before a conclusion can be made.

C

Preliminary evidence of benefit of NAC for adrenoleukodystrophy has been found. Further well-designed research is required before a conclusion can be made.

C

Limited human study investigating the effect of NAC on Alzheimer's disease has shown improvement in one assessment of memory and a lack of effect on others. Additional well-designed trials are needed before a conclusion can be made.

C

Limited study showed a lack of benefit of NAC in patients with amyotrophic lateral sclerosis. Further study is needed.

C

Results of studies on the effect of NAC on angina are mixed. Further well-designed clinical trials are needed before a conclusion may be made.

Although not well-studied in humans, NAC has been shown to have a possible anti-cancer effect. However, preliminary human study reported a lack of benefit of NAC in increasing survival time of cancer patients. Additional research is needed before firm conclusions can be made.

C

Limited study suggests that NAC may decrease side effects of chemotherapy. However, results from different studies conflict. Further well-designed clinical trials are required.

C

There is a lack of sufficient evidence to make a conclusion on the use of NAC to treat chronic lung disease in infants. Preliminary human study suggests a lack of benefit of NAC in this group. Further study is required in this area.

C

There is a lack of sufficient evidence to make a conclusion regarding the use of NAC in the treatment of chronic obstructive lung disease. Well-designed clinical trials are needed.

C

Limited study showed that NAC may decrease the desire to use cocaine in cocaine-dependent patients. Well-designed study is needed before firm conclusions may be made.

C

In preliminary study, patients with bipolar disorder had decreased symptoms of depression when NAC was used together with standard treatment. Further well-designed study is required before a conclusion can be made.

C

Preliminary study suggests that NAC may be ineffective in treatment of high-altitude appetite reduction. Further study is required before a conclusion can be made.

C

Preliminary research suggests that eye drops containing NAC may help treat dry eye syndrome. Further research is required.

C

Antioxidants may decrease exercise-associated muscle pain and fatigue and, thus, may increase exercise endurance. In limited study, NAC increased exercise endurance. Further well-designed research is required before a conclusion may be made.

C

Preliminary research showed that NAC lacked benefit as an adjunct to a fertility drug in women with unexplained infertility. Further research is required before a conclusion may be made.

C

NAC has been investigated for its potential to protect against heart damage following coronary artery bypass grafting (CABG). The clinical effects of NAC were unclear. Further research is required before firm conclusions may be made.

C

Although not well-studied in humans, NAC treatment was found to reduce the degree of Helicobacter pylori infection. Limited human research suggests NAC may provide additional benefit to antibiotic-treated patients infected with Helicobacter pylori. Further well-designed clinical trials are required before a conclusion may be made.

C

The results of limited study on the effect of NAC on HIV/AIDS are unclear. Additional research is needed.

C

High blood levels of homocysteine may increase the risk of heart disease. Preliminary human study showed that NAC decreased homocysteine levels in patients with high blood levels of homocysteine, in patients with kidney disease, and in healthy people. It is unclear if NAC decreases the risk of heart disease. Well-designed studies are required before conclusions may be made in this area.

C

Results of different studies investigating the effect of NAC on reducing levels of certain blood lipids conflict. Further evidence is required before a conclusion may be made.

C

Limited human study suggests that regular NAC use may help prevent influenza. Additional research is needed.

C

In limited human research, NAC failed to help patients with malaria. Further research is needed before a conclusion may be made.

C

In limited research, NAC improved sperm concentration in infertile males. Further research is required.

C

In women with a history of miscarriages, NAC plus folate decreased the rate of miscarriage compared with folate treatment alone. Additional study is needed.

C

Results of preliminary study suggest NAC may not prevent multiple organ failure. Further well-designed studies are required before a conclusion may be made.

C

Results of preliminary research suggest that NAC may help patients who have had a heart attack. Well-designed human studies are needed before conclusions can be made.

C

In preliminary research, NAC reduced the frequency and severity of daytime nosebleed. Further research is needed.

C

Preliminary study showed a lack of benefit of NAC in liver transplantation. Further research is required before a conclusion may be made.

C

Results of study of NAC for osteoporosis/post-menopausal bone loss are unclear. Further well-designed research is required before a conclusion may be made.

C

In limited study, NAC lacked benefit for pancreatitis prevention. Further information is required in this field.

C

There is limited human study on the use of NAC for peripheral artery disease. Further well-designed research is required before a conclusion may be made.

C

In preliminary study, an oral rinse containing NAC reduced plaque formation. Further research is required.

C

Limited evidence suggests NAC may increase ovulation and pregnancy and improve insulin levels in women with polycystic ovarian syndrome (PCOS). Results are mixed, however, and further research is needed.

C

NAC has been investigated for its potential in aiding recovery from heart surgery. Further research in this field is warranted.

C

NAC has been studied for its possible benefit in reducing preterm labor in pregnant women with a previous history of preterm labor. Further research is needed in this field before a conclusion may be made.

C

In preliminary research, NAC has been investigated as a treatment for schizophrenia. Further well-designed research is required before a conclusion may be made.

C

There is limited human study on the use of NAC for sepsis treatment. Further evidence is needed.

C

There is a lack of sufficient evidence to make a conclusion for or against the use of NAC in the treatment of Sjögren's syndrome. Well-designed clinical trials are required.

C

Limited study showed a lack of effect of NAC on hearing in people exposed to loud noise. Further research is required in this field.

C

NAC has been investigated as a treatment for ulcerative colitis. Further well-designed research is required.

C

There is fairly strong evidence suggesting that NAC is not useful in the treatment of cystic fibrosis. Well-designed studies are needed to make a firm conclusion.

D

Available evidence suggests NAC is ineffective for erythropoietic protoporphyria. Further evidence is required before a firm conclusion may be made.

D

There is fairly strong evidence that NAC does not increase a hepatitis patient's response to interferon therapy. Additional research is needed.

D

Until further information is available, there is a lack of sufficient evidence for or against the use of NAC for the prevention of kidney damage. More research is needed.

D

* Key to grades

A: Strong scientific evidence for this useB: Good scientific evidence for this useC: Unclear scientific evidence for this useD: Fair scientific evidence for this use (it may not work)F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Note: Intravenous or inhaled N-acetyl cysteine (NAC) should be used only under the supervision of a health care provider. All patients should consult a healthcare provider before starting any treatment.

For acetaminophen toxicity, an initial dose of 140 milligrams per kilogram NAC has been taken by mouth, followed by 70 milligrams per kilogram every four hours for 72 hours or until serum levels of acetaminophen were undetectable. A loading dose of 140-150 milligrams per kilogram body weight of NAC, followed by 50-70 milligrams per kilogram over four hours, with or without 100 milligrams per kilogram over 8-16 hours (or until serum acetaminophen levels were undetectable), has been used parenterally.

For acute respiratory distress syndrome, 150 milligrams per kilogram body weight of NAC has been delivered intravenously over 20 minutes the first day, followed by 50 milligrams per kilogram daily for three days.

For acute respiratory infections, 200-230 milligrams of NAC has been taken by mouth two to three times daily for 6-15 days.

For addiction to gambling, 600 milligrams of NAC, increasing every two weeks to a dose of 1,800 milligrams, has been taken by mouth for up to 14 weeks.

For angina, 2 grams of NAC in 100 milliliters of saline has been delivered intravenously over 15 minutes, followed by 5 milligrams per kilogram body weight per hour over 30 hours, as has 5 grams of NAC in 200 milliliters of 5% dextrose infused over 15 minutes, every six hours over a period of 24 hours.

For asthma, 0.5% nebulized NAC has been inhaled.

For exercise performance enhancement,125 milligrams per kilogram body weight of NAC per hour has been infused intravenously for 15 minutes, followed by 25 milligrams per kilogram body weight per hour for 20 minutes prior to and throughout exercise.

For sulfur mustard-induced bronchiolitis (swelling in the small air passages of the lungs), 1,200-1,800 milligrams of NAC has been taken by mouth in two or three divided doses daily for four months.

For chemotherapy adverse events, 5.5 grams per square meter body mass of NAC has been taken by mouth one hour before doxorubicin therapy every four weeks until the doxorubicin dose reached 300-350 milligrams per square meter or 500-550 milligrams per square meter. NAC at a dose of 1,200 milligrams has been taken by mouth 1.5 hours prior to oxaliplatin for 12 treatment cycles, with fluorouracil and leucovorin.

For chronic bronchitis, 200-600 milligrams of NAC has been taken by mouth twice daily for up to six months, as well as 300 milligrams of NAC in controlled-release tablets twice daily for six months.

For chronic obstructive pulmonary disease, 600 milligrams of NAC has been taken by mouth daily for six months.

For cocaine withdrawal, 600 milligrams of NAC has been taken by mouth every 12 hours for a total of four doses.

For depression, 1 gram of NAC has been taken by mouth twice daily for 24 weeks.

For diminished appetite (high-altitude anorexia), 400 milligrams of NAC has been taken by mouth daily with breakfast.

For dry eye syndrome, 20% NAC ophthalmic solution every two hours has been applied to the affected eye.

For female infertility, 1,200 milligrams of NAC has been taken by mouth daily for five days starting at day two or three of the menstrual cycle. Patients were also using clomiphene citrate.

For heart protection during coronary artery bypass grafting (CABG), an induction cardioplegia solution containing 4 millimoles per liter of NAC, and a maintenance cardioplegia solution containing 2 millimoles per liter of NAC has been delivered through a catheter. Also studied was a dose of 300 milligrams of NAC added to intermittent antegrade blood cardioplegia. Fifty milligrams per kilogram body weight NAC has been added to cold blood cardioplegia. For one hour before the procedure a dose of 50 milligrams per kilogram body weight has been intravenously infused, followed by intravenous infusion for 48 hours after the operation at a dose of 50 milligrams per kilogram body weight daily.

For Helicobacter pylori infection, 10 milliliters (400 milligrams) of NAC has been taken by mouth three times daily for 10 days with clarithromycin and lansoprazole.

For hyperhomocysteinemia (high blood levels of homocysteine), 600 milligrams of NAC has been taken by mouth daily for eight weeks. Five grams of NAC (Hidonac®) in 500 milliliters of 5% glucose has been intravenously infused for four hours in patients with end-stage kidney disease.

For influenza prevention, 600 milligrams of NAC effervescent tablets have been taken by mouth twice daily for six months.

For male infertility, 600 milligrams of NAC has been taken by mouth daily for 26 weeks.

For miscarriage prevention, 600 milligrams of NAC plus folic acid has been taken by mouth daily up to week 20 of gestation or miscarriage.

For myocardial ischemia (decreased blood flow to the heart), 100 milligrams per kilogram body weight NAC with streptokinase has been used intravenously six times daily. A loading dose of 20 milligrams per minute of NAC for one hour, followed by 10 milligrams per minute for 23 hours with streptokinase and nitroglycerine, has been delivered parenterally. A dose of 150 milligrams per kilogram body weight of NAC in 250 milliliters of 5% dextrose over 30 minutes or 15 grams over 24 hours with streptokinase has also been used.

For nosebleed, 600 milligrams of NAC has been taken by mouth three times daily for 12 weeks.

For pancreatitis, 600 milligrams of NAC has been given by mouth at 12 and 24 hours prior to endoscopic retrograde cholangiopancreatography, followed by 600 milligrams given intravenously twice daily for two days following the procedure. Six hundred milligrams of NAC has been administered intravenously 12 and 24 hours prior to endoscopic retrograde cholangiopancreatography, followed by 600 milligrams twice daily for two days after the procedure.

For plaque formation, 4 milliters of a 10% aqueous solution has been used in the mouth.

For polycystic ovarian syndrome, 1.2 grams of NAC has been taken by mouth daily, starting on day three of the menstrual cycle, for five days with clomiphene citrate. Another dose taken by mouth was 1.8-3 grams of NAC daily for 5-6 weeks.

For recovery after heart surgery, 600 milligrams has been taken by mouth the day before surgery, followed by a bolus of 150 milligrams per kilogram body weight delivered intravenously before skin incision, followed by perfusion at 12.5 milligrams per kilogram per hour for 24 hours.

For pregnancy support, 600 milligrams of NAC plus 17-hydroxyprogesterone caproate has been taken by mouth daily until 36 weeks of pregnancy or active labor.

For schizophrenia, two 500-milligram capsules of NAC have been taken by mouth twice daily for 24 weeks.

For sepsis, 150 milligrams per kilogram body weight NAC has been infused over 15 minutes, followed by a continuous infusion of 50 milligrams per kilogram body weight over four hours.

For Sjögren's syndrome, 200 milligrams of NAC has been taken by mouth three times daily for four weeks.

For ulcerative colitis, 800 milligrams has been taken by mouth daily for four weeks, in addition to mesalamine.

Children (under 18 years old)

Note: Intravenous N-acetyl cysteine (NAC) should be used only under the supervision of a health care provider. All patients should consult a healthcare provider before starting any treatment.

For acetaminophen toxicity, a loading dose of 140 milligrams per kilogram body weight of NAC, followed by 70 milligrams per kilogram body weight every four hours for 72 hours or until serum levels of acetaminophen were undetectable, has been taken by mouth. A loading dose of 150 milligrams per kilogram body weight of NAC over 15 minutes, followed by 50 milligrams per kilogram body weight over four hours, and then 100 milligrams per kilogram body weight for 16 hours (total duration varies) has been used parenterally.

For acute respiratory infection, 300-600 milligrams (depending on age) has been taken by mouth for eight days. A dose of 100-300 milligrams (depending on age) has been taken by mouth for six days.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid with known allergy or hypersensitivity to N-acetyl cysteine (NAC) and related substances.

There have been reports of patients developing an anaphylactic-like reaction to NAC. Features of the anaphylactic-like reaction include rash, swelling under the skin, low blood pressure, and bronchospasm. Hives have also been reported.

Side Effects and Warnings

NAC is generally well tolerated and regarded as safe. Most side effects of NAC resulted at single doses of greater than 9 grams when part of a daily regime of greater than 30 grams daily. The most common side effects in humans include diarrhea, nausea, vomiting, and headache.

Patients treated for acetaminophen toxicity with NAC have died secondarily to questionable NAC overdose. Intravenous or inhaled NAC should only be used under a physician's care. All patients should consult with a healthcare provider before starting any treatment.

There have been reports of patients developing an anaphylactic-like reaction to NAC. Features of the anaphylactic-like reaction include rash, swelling under the skin, low blood pressure, and bronchospasm. Hives have also been reported.

NAC may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

NAC may increase blood pressure. Caution is advised in patients with blood pressure disorders or in those taking drugs, herbs or supplements that affect blood pressure.

NAC may increase blood sugar levels. Caution is advised in patients with diabetes, hyperglycemia or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

Use with caution in patients with heart disease, due to increased risk of changes in heart function, such as palpitations and rapid heartbeat.

Use with caution in patients with gastrointestinal disorders, due to the risk of increased gastrointestinal symptoms.

Use with caution in patients with respiratory disorders, due to a potential for increased respiratory symptoms such as wheezing, shortness of breath, cough, and sputum (phlegm) production.

Use with caution in patients using antibiotics, due to theoretical negative interactions.

Use with caution in patients needing charcoal treatment, as charcoal may reduce NAC absorption and efficacy.

Use with caution in patients using nitroglycerin, due to a potential for increased headaches and coronary dilation.

Use with caution in zinc-deficient patients, due to possible decreased zinc absorption with high doses of NAC.

Use with caution in patients with unpleasant mood, due to a potential for increased symptoms.

Use with caution in patients complaining of dizziness, lightheadedness, or with visual complaints, due to a potential for increased symptoms.

Avoid in patients with allergy or hypersensitivity to NAC. NAC should be used in allergic patients only when medical personnel consider it necessary.

Avoid use of doses greater than 30 grams daily.

Avoid in pregnant or breastfeeding women due to a lack of safety data. NAC has been used for acetaminophen toxicity in pregnant women.

Pregnancy and Breastfeeding

Avoid in pregnant or breastfeeding women due to a lack of safety data. NAC has been used for acetaminophen toxicity in pregnant women.

NAC may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

NAC may increase blood sugar levels. Caution is advised when using medications that affect blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

NAC may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

NAC may increase blood sugar levels. Caution is advised when using herbs or supplements that affect blood sugar levels. Blood glucose levels may require monitoring, and doses may need adjustment.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.